Postpartum depression (PPD) is a serious mental illness that affects more than 500,000 US women every year. In addition to the suffering experienced by women, it has profound effects on women's families and their developing infants. Despite the public health significance of PPD, relatively little research has been conducted to determine which treatments are efficacious. There have been no placebo-controlled trials using antidepressant medication for the entire range of depression severity of PPD. Consequently, the efficacy of antidepressants for PPD is unknown. In contrast, Interpersonal Psychotherapy (IPT) has been more thoroughly studied for the treatment for PPD. Although there is evidence supporting the efficacy of IPT compared to a waiting list control, IPT for PPD has not yet been compared to either placebo or antidepressant medication. To address this lack of data, we propose to conduct a randomized clinical trial with a representative sample of 300 outpatients with PPD recruited from the community, from clinics, and from a Postpartum Day Hospital at two sites in Iowa and Rhode Island. The aim of this project is to compare the efficacy of three treatment conditions: 1) Pharmacotherapy alone (Sertraline + Clinical Management); 2) IPT alone; and 3) Placebo (Pill Placebo + Clinical Management). We hypothesize that both sertraline and IPT will be significantly more efficacious than placebo with respect to depressive symptomatology and social functioning at the end of the 12-week trial. In addition to investigating this acute outcome, we will also examine the efficacy of the two active treatments using a non-inferiority test to compare treatment with IPT and sertraline. We will also examine the specific effects of the active treatments. Since anxiety is a common feature of PPD, we will test the hypothesis that treatment with sertraline will be significantly more efficacious than IPT and placebo in reducing anxiety symptoms. Since IPT is specifically designed to address interpersonal functioning and social support, we will test the hypothesis that IPT will be more efficacious than sertraline and placebo in improving social functioning. The study is highly relevant to the public health of women and their families. Findings from the proposed research will provide empirical data in support of treatments for PPD, and will therefore have a significant impact on the clinical management of PPD. The data from this study will also improve the ability of women and their physicians to make informed risk/benefit decisions about their postpartum mental health care.